Kunihiko Nagakari

Activated protein C improves the visceral microcirculation by attenuating the leukocyte-endothelial interaction in a rat lipopolysaccharide model

Objective:Abnormalities in the vascular endothelial function play an important role in the development of septic organ dysfunction. The aim of the study was to examine the effect of recombinant human activated protein C on leukocyte-endothelial interaction in endotoxemia. Design:Experimental animal model of sepsis. Setting:University research laboratory. Subjects:Normal Wistar rats. Each animal was infused with 4.5 mg/kg lipopolysaccharide to simulate severe sepsis. Interventions:Rats were injected with endotoxin simultaneously with either a low or a high dose of recombinant human activated protein C (n = 7). One, 2, and 3 hrs after injection, mesenteric microcirculation was observed under intravital microscopy. In another series, tumor necrosis factor, interleukin-6, alanine transaminase, and blood urea nitrogen levels were evaluated (n = 5). Measurements and Main Results:The adhesive leukocyte count on the endothelium was significantly suppressed in both high-dose and low-dose groups (p < .01 and .05, respectively). The bleeding events decreased in the low-dose treatment group compared with both the control (p < .05) and high-dose group (p < .05). Microcirculatory flow as expressed by red blood cell velocity was maintained better in the low-dose group. Comparison of cytokine levels showed a significant decrease in the treatment groups. Organ damage markers were also suppressed in the treatment groups (p < .05) Conclusions:Recombinant human activated protein C demonstrated a protective effect on microcirculation through the inhibition of leukocyte-endothelial interaction and suppression of inflammatory cytokine production.

Single-incision laparoscopic colectomy for colon cancer: early experience with 31 cases.

BACKGROUND: Transumbilical single-port surgery has been developed with the aim to further reduce the invasiveness of conventional laparoscopy. OBJECTIVE: This study aimed to report our experience with 31 patients who were treated with transumbilical single-incision laparoscopic colectomy for colon cancer. DESIGN: This is a retrospective review of prospectively gathered data. SETTINGS: This study was conducted at the Department of Surgery of Juntendo University Urayasu Hospital between April 2009 and April 2010. Data were obtained from a prospectively maintained single-institution laparoscopic colon cancer database. PATIENTS: Thirty-one consecutively selected patients (mean BMI, 22.5 ± 2.3) were evaluated. INTERVENTIONS: All patients underwent single-incision laparoscopic colectomy for colon cancer. Two different approaches were used for single-incision laparoscopic colectomy: the trocar insertion method and the SILS port method. The trocar insertion method was adopted in 22 of 31 patients, and the SILS port method was used in 9 patients. MAIN OUTCOME MEASURES: The main measures of outcomes were intraoperative findings, postoperative course, and oncological outcomes. RESULTS: The most common procedure was sigmoid colon resection performed in 12 of 31 (39%) patients. The mean skin incision was 2.72 ± 0.79 (range, 3–5) cm. The operating time ranged from 101 to 263 (mean, 156 ± 45) minutes. The volume of bleeding ranged from 5 to 60 (mean, 27 ± 19) mL. No intraoperative complications were observed in this series. Postoperatively, there was no mortality. Wound infection was observed in 1 patient. The number of harvested lymph nodes was 18 ± 2.1, and the mean tumor-free resection margin was 11 ± 4.8 cm. CONCLUSION: Our experience indicates that single-incision laparoscopic colectomy is feasible for selected patients with colon cancer.

Laparoscopy-Assisted Low Anterior Resection with a Prolapsing Technique for Low Rectal Cancer

Laparoscopy-assisted low anterior resection (LAR) for low rectal cancer is a difficult procedure, presenting problems with rectal washout, selecting the appropriate distal transection line, and achieving safe anastomosis. To resolve these problems, we used a prolapsing technique to perform laparoscopy-assisted LAR. Total mesorectal excision (TME) is performed laparoscopically. The proximal colon is transected laparoscopically with the aid of an endoscopic stapler, and the distal rectum, including the lesion, are everted and pulled transanally to outside the body. Only washout of and wiping off the distal rectum and intestinal resection are performed extracorporeally. The distal rectum is pushed back through the anus into the pelvis, and intracorporeal anastomosis is completed laparoscopically with a double-stapling technique. Our limited experience suggests that the prolapsing technique helps to prevent problems with laparoscopy-assisted LAR in selected patients with low rectal cancer.

Comparison of Two Different Energy-Based Vascular Sealing Systems for the Hemostasis of Various Types of Arteries: A Porcine Model—Evaluation of Ligasure ForceTriad™

BACKGROUND The ForceTriad™ generator has been recently developed. This new electrosurgical generator would demonstrate improved quality and efficiency in blood vessel sealing. AIM To compare currently available 10-mm laparoscopic electrosurgical devices with the LigaSure™ Vessel Sealing System and ForceTriad generator (Valleylab, Inc., a division of Tyco Healthcare) for use in vessel sealing. METHODS Blood vessels of various types and diameters were harvested from alive four pigs using three instruments: LigaSure Atlas™ with LigaSure Vessel Sealing Generator (LSAt), LigaSure Atlas with ForceTriad Generator (LSAtFT), and Endoclip™ II (Autosuture, USSC; a division of Tyco Healthcare). A total of 100 arteries were processed by removal of fatty and connective tissue from the adventitia before sealing. An additional set of specimens was sealed and histopathologically analyzed after being stained with hematoxylin and eosin. RESULTS The mean burst pressure was significantly higher with LSAtFT compared to LSAt (P < 0.01). The sealing process was significantly shorter with LSAtFT (P < 0.05). With regard to the degree of thermal injury, adventitial collagen denaturation and proximal thermal injury to the smooth muscle in the media of the vessel wall were less common with LSAtFT; however, the numbers were too small for statistical analysis. CONCLUSION Both the LSAt and LSAtFT secured all vessel sizes to well above physiologic levels. The LSAtFT could be used more confidently in vessels up to 7 mm. Our findings indicate that LSAtFT could be a safer and more efficient instrument for advanced laparoscopic surgery.

Kinetics of cytokines and PMN-E in thoracoscopic esophagectomy

BACKGROUND Perioperative increases in the levels of cytokines and polymorphonuclear leukocyte elastase (PMN-E) have been shown to be related to degree of surgical trauma. METHODS We measured the changes in levels of interleukin-6 (IL-6), interleukin-8 (IL-8), and PMN-E in the perioperative period in patients undergoing thoracoscopic esophagectomy (n = 15) and conventional transthoracic esophagectomy (n = 15) for thoracic esophageal cancer. RESULTS Both IL-6 and IL-8 increased markedly immediately after transthoracic esophagectomy and thereafter, but only a slight increase was observed after the thoracoscopic procedure (IL-6: p = 0.047; IL-8: p = 0.03). A difference was also seen in the pattern of changes in PMN-E. Levels of PMN-E increased immediately after transthoracic esophagectomy and continued to be high up to the 3rd postoperative day, but they remained low after the thoracoscopic procedure and showed no increase (p <lt; 0.01). CONCLUSION These results suggest that, compared with transthoracic esophagectomy, thoracoscopic esophagectomy results in less production of cytokines and PMN-E and thus causes less surgical trauma.

Laparoscopic one-stage resection of right and left colon complicated diverticulitis equivalent to hinchey stage I–II

PurposeThe safety and effectiveness of laparoscopic surgery is well established for recurrent, uncomplicated diverticular disease, but not for complicated diverticular disease. Using the Hinchey classification, we compared laparoscopic colon resection (LAPH) with conventional open colon resection (OPH) for the treatment of complicated diverticulitis equivalent to Hinchey stage I–II.MethodsIn this study, the Hinchey classification (I–IV) was also adopted for right-sided diverticulitis (I′–IV′). We reviewed the clinical records of 58 patients who underwent colon resection for complicated colon diverticulitis (Hinchey stage I–IV or I′–IV′) between May 1994 and December 2008. Fifty-two patients underwent colon resection for Hinchey I–II or I′–II′ disease; as LAPH in 36 and as OPH in 16. Only one patient required conversion to the open procedure after laparoscopy.ResultsThe overall complication rate was significantly higher in the OPH group (43.8%) than in the LAPH group (16.7%; P < 0.05). Wound infection was significantly more common in the OPH group (37.5%) than in the LAPH group (11.1%; P < 0.05). Hospital stay was significantly shorter in the LAPH group (P < 0.05). Hartmann procedure was performed in one patient from each group. No anastomotic leakage occurred in either group.ConclusionOur findings indicate that laparoscopic surgery can be performed safely and effectively even for patients with Hinchey I–II, I′–II′ colonic diverticulitis.

The effect of plasma-derived activated protein C on leukocyte cell-death and vascular endothelial damage

INTRODUCTION The role of leukocyte and its death in the progression in inflammation attracts attention nowadays. The purpose of this study is to examine the effects of activated protein C (APC) on leucocyte cell death and vascular endothelial damage in sepsis. METHODS Wistar rats were infused with lipopolysaccharide (8.0mg/kg) concomitantly with either a low dose (0.5mg/kg), a high dose (5.0mg/kg) of plasma-derived APC or albumin. One and 3hours after the injections, the mesenteric microcirculation was observed by intravital microscopy. The serum levels of nucleosome and High Mobility Group Box 1 (HMGB1) were measured in each group. In another series, cultured leukocyte cell-death in the medium supplemented with serum obtained from each group was examined in vitro. RESULTS Microcirculatory disturbance was significantly suppressed in both the high-dose and low-dose groups compared to the control group (P<0.01, 0.05, respectively). The bleeding area was significantly increased in the control and high-dose groups (P<0.05, 0.01, respectively). Serum levels of cell death markers such as nucleosome and HMGB1 were significantly decreased in the treatment groups (P<0.01), and the protective effect was more pronounced in high-dose group. Cell death suppression was most prominent in high-dose group and the formation of neutrophil extracellular traps (NETs) was significantly suppressed in the treatment groups. CONCLUSION Low-dose plasma-derived APC exerted protective effects on the microcirculation without increasing the risk of bleeding. The protective effect against leukocyte cell death and the suppressive effect on NETs formation of APC might be related to its beneficial effects.

Natural orifice specimen extraction using prolapsing technique in single-incision laparoscopic colorectal resections for colorectal cancers

It is often technically difficult to cut the lower rectum with an endoscopic linear stapler in single‐incision laparoscopic colorectal resections (SILC) because some surgical devices are inserted through the same access platform. If the rectum is cut incorrectly, it may cause anastomotic leakage. We recently applied natural orifice specimen extraction (NOSE) using the prolapsing technique to overcome this technical difficulty in SILC procedures in selected patients.

Intermittent low-dose cisplatin infusion as a possible modulator of 5-fluorouracil

BackgroundThis study was designed to determine whether 5-fluorouracil combined with intermittent low-dose cisplatin (cis-diaminedichloroplatinum, CDDP), a 5-fluorouracil modulator, would be an effective antitumor regimen.MethodsSarcoma 180 tumor (mouse sarcoma) was implanted in mice, and intravenous CDDP injections (0.5 mg/kg) were given at intervals of 12 hours. Tumors were removed on days 1, 3, and 5 of treatment for quantification of the tumor tetrahydrofolate and blood platinum levels. One group of mice was treated with a combination of CDDP and 5-fluorouracil (10 mg/kg), and another group was treated with 5-fluorouracil alone. Tumor thymidylate synthetase levels and tumor weights were compared between these 2 groups.ResultsBlood total platinum levels rose as the number of doses increased, while the tumor tetrahydrofolate levels did not change. Neither the levels of thymidylate synthetase, nor tumor reduction, differed between the CDDP/5-fluorouracil and the 5-fluorouracil treatment groups.ConclusionNo significant effect of intermittent low-dose CDDP therapy was seen on folic acid or thymidylate synthetase levels, or on tumor growth. The results of this study do not endorse the efficacy of intermittent low-dose CDDP as a modulator of 5-fluorouracil.

Prothrombin Time Tests for the Monitoring of Direct Oral Anticoagulants and Their Evaluation as Indicators of the Reversal Effect

Introduction: The prompt assessment and the reversal of direct oral anticoagulants (DOACs) are urgent matters in the emergency care setting. Thus, we planned to elucidate the adequate prothrombin time (PT) test for the evaluation of the anticoagulant effects of various DOACs. Methods: The anticoagulant effects of rivaroxaban, apixaban, and edoxaban were measured with 3 PT tests (Triniclot PT Excel S, Neoplastin R, and Thromborel S). Human plasma was spiked with each DOAC at a range of 0 to 1000 ng/mL, and the PT was measured using each PT test. In another series, the reversal effect of either 4-factor prothrombin complex concentrate (PCC) or activated PCC (aPCC) was evaluated with each PT test. Results: All PT reagents correlated with the concentrations of each DOAC, however, the reactivity was considerably different between the DOACs and the PT tests. A prolonged PT with DOACs was reversed both by PCC and aPCC in a dose-dependent manner; however, Triniclot PT Excel S showed reprolongation of the PT with a higher dose of PCC. Conclusion: The proper choice of PT test is necessary for the assessments of the anticoagulant activity of DOACs. It is also important to understand the different characteristics of each PT test for the assessment of the reversal effects of PCC.